The University of Pittsburgh proposes to continue a Specialized Program of Research Excellence (SPORE) in Head and Neck Cancer. The overall goals of the Head and Neck SPORE are to improve the prevention and treatment of head and neck cancer as well as the detection and treatment of thyroid cancer (new in this renewal). The SPORE program consists of four translational research projects, 3 focused on head and neck squamous cell carcinoma (HNSCC) and one focused on thyroid cancer, two research cores, an administrative core, a developmental research program and a career development program. The SPORE will use an interdisciplinary approach to meet its objectives by carrying out projects jointly led by investigators in basic, applied and clinical science. The long-term goal of the Head and Neck SPORE is to conduct clinical studies based on research results from the translational research projects that will serve as the basis for improving the outcome of individuals diagnosed with head and neck cancers. The four main projects include: (1) Chemoprevention of Head and Neck Cancer; (2) Optimization of STAT3 Decoy Delivery for Head and Neck Cancer Treatment; (3) Checkpoint Receptor Targeting to Enhance Cetuximab Efficacy Against HNSCC; and (4) Molecular-Guided Risk Stratification of Thyroid Nodules and Cancer. The three cores will interact closely to assist the main research projects, developmental research projects and career development investigators in carrying out translational head and neck cancer research. The research cores include: (a) Histology/Tissue and (b) Informatics, Biostatistics and Bioinformatics. The Administrative Core will solicit feedback from the Internal and External Scientific Advisory Boards and provide scientific, regulatory and fiscal oversight for the SPORE program. The Head and Neck SPORE investigators will work together to synergistically achieve the goals of the program and will also continue to interact closely with investigators from other Head and Neck and Thyroid SPOREs at other institutions, as well as the cooperative groups, to improve the outcome of patients with cancers of the head and neck.